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Skeletal muscle structure and function in COPD

Institution: University of California, San Diego
Investigator(s): Timothy Gavin, Ph.D.
Award Cycle: 1999 (Cycle 8) Grant #: 8KT-0081 Award: $224,842
Subject Area: Pulmonary Disease
Award Type: New Investigator Awards

Initial Award Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction. COPD predominantly encompasses chronic bronchitis, and emphysema. In the United States, COPD affects up to 15 million people. While the mortality rates associated with other common diseases, such as cardiovascular diseases and stroke, have declined over the past 20 years, the mortality rate for COPD rose nearly 33% from 1979 to 1991. Cigarette smoking is the major factor associated with the development of COPD. Poor exercise tolerance is a serious problem in patients with COPD. The predominant cause of this exercise limitation is the airflow obstruction present in COPD. Recent evidence suggests that the exercising skeletal muscle may also be impaired in patients with COPD. However, the prevalence of this skeletal muscle dysfunction and the mechanisms responsible for it are not well understood. Quite often, skeletal muscle dysfunction has been evaluated while patients are performing large muscle mass exercise such as stationary bicycle exercise. This form of exercise and subsequent skeletal muscle evaluation is inappropriate in COPD due to the large limitation in supplying oxygen to the blood resultant from the airflow obstruction. This proposal is designed to provide the most comprehensive data to date evaluating skeletal muscle function using a single leg and performing kick exercise, similar to leg extension exercise often seen in health clubs. By using this relatively small muscle mass, the limitation created by the airflow obstruction in these patients can be removed. This form of exercise provides the means to evaluate the limits to oxygen utilization in the exercising muscle of COPD patients. One potential limitation to oxygen utilization by the working skeletal muscle is the number of blood vessels, known as capillaries, surrounding the muscle fibers. The more contact present between the muscle fibers and the capillaries, the greater potential for oxygen to get to the exercising muscles. In order to evaluate the number of capillaries surrounding the muscle fibers, muscle biopsies will be taken. The results from these muscle biopsies will be evaluated with the data from the leg kick exercise to determine the role of skeletal muscle capillarization in exercise limitation in COPD. Vascular endothelial growth factor (VEGF) is a protein produced by the body which promotes the growth of new capillaries. Recently, exogenous administration of VEGF has been shown to promote new blood vessel formation in patients with coronary heart disease. Aerobic exercise training is known to induce capillary growth in normal exercising skeletal muscles. Exercise has been shown to increase VEGF in the skeletal muscles of both animals and humans. It is believed that this increase in VEGF is important in the capillary growth associated with exercise training. The muscle biopsy samples will also be used to evaluate if the increase in VEGF normally observed in response to exercise is impaired in patients with COPD. Finally, COPD patients will be exercise trained for eight weeks using single leg exercise. After successful completion of the exercise training, skeletal muscle structure and function will again be examined using single leg exercise and muscle biopsies.

VEGF receptor (Flt-1) and nitric oxide synthase inhibition
Periodical: FASEB Journal Index Medicus:
Authors: Gavin TP, Wagner H, Wagner PD ART
Yr: 2000 Vol: 13 Nbr: 5 Abs: A352 Pg:

VO2 responses to running and cycling
Periodical: Medicine and Science in Sports and Exercise Index Medicus:
Authors: Updyke RS, Stephens LP, Blumoff SA, et al ABS
Yr: 2000 Vol: 32 Nbr: 5 Abs: S221 Pg:

VEGF receptor (flk-1) mRNA response to acute exercise
Periodical: Medicine and Science in Sports and Exercise Index Medicus:
Authors: Gavin TP, Wagner PD ABS
Yr: 2000 Vol: 32 Nbr: 5 Abs: S103 Pg:

Pulmonary gas exchange during exercise in women: effect of exercise type and work increment
Periodical: Journal of Applied Physiology Index Medicus:
Authors: Hopkins SR, Barker RC, Brutsaert TD, et al ART
Yr: 2000 Vol: 89 Nbr: 2 Abs: Pg: 721-730

The effect of short-term exercise training on angiogenic growth factor responses in rats
Periodical: Journal of Applied Physiology Index Medicus:
Authors: Gavin TP, Wagner PD ART
Yr: 2001 Vol: 90 Nbr: 4 Abs: Pg: 1219-1226

Ethanol increases VEGF mRNA in rat skeletal muscle
Periodical: FASEB Journal Index Medicus:
Authors: Gavin TP, Wagner PD ABS
Yr: 2001 Vol: 14 Nbr: 4 Abs: A794 Pg:

Thermal response to exercise in moderate heat is unaffected by clothing fabric.
Periodical: Medicine and Science in Sports and Exercise Index Medicus:
Authors: Gavin, TP, Babington, JP, Harmes, CA, Ardelt, ME, Tanner, DA, and Stager, JM ART
Yr: 2001 Vol: 33 (12) Nbr: Abs: Pg: 2124-2130

Acute ethanol increases angiogenic growth factor gene expression in rat skeletal muscle.
Periodical: Journal of Applied Physiology Index Medicus:
Authors: Gavin, TP, and Wagner, PD ART
Yr: 2002 Vol: 92 Nbr: Abs: Pg: 1176-1182

Clothing and thermoregulation during exercise
Periodical: Sports Medicine Index Medicus:
Authors: Gavin TP ART
Yr: 0 Vol: Nbr: Abs: Pg:

Reduced mechanical efficiency in COPD, but normal peak VO2 with small muscle mass exercise.
Periodical: American Journal of Critical Care Medicine Index Medicus:
Authors: Richardson RS, Leek BT, Gavin TP, Haseler LJ, Mudaliar SRD, Henry R, Ries AL, et al. ART
Yr: 0 Vol: Nbr: Abs: Pg: